Single-molecule light scattering using optical holography

• Scientists from the Kukura group at Oxford Chemistry have detected ultra-weak light scattering from single protein molecules using optical holography.
• Published today in Nature Photonics, their new approach increases the sensitivity of the technique by five orders of magnitude compared to the current state of the art.
• This breakthrough paves the way for wider exploration of biomolecular interactions and applications in nanoscience.

University of Oxford: Single-molecule light scattering using optical holography.

While all materials scatter light, the minuscule scattering from individual molecules has remained invisible to holographic techniques until now. Holographic methods – optical microscopic techniques that rely on light scattering – provide many advantages over traditional intensity measurements in terms of information content, tunability and post-processing. Previous techniques have, however, struggled to capture faint signals from individual molecules, limiting progress in label-free single-molecule studies.

Overcoming these limitations, scientists from the Kukura group at Oxford Chemistry have demonstrated detection of the ultra-weak light scattering from single proteins using optical holography. Their study, published today in Nature Photonics, introduces a transformative approach by combing dark-field scattering microscopy with a Mach-Zehnder interferometer.

Splitting light emerging from the sample and coupling it with a reference before splitting the detection into four parallel channels, researchers have increased the technique’s sensitivity by five orders of magnitude compared to the current state of the art in terms of interaction strength. This enables precise detection and measurement of single proteins.

The team’s breakthrough not only enables direct measurement of molecular polarizability and sample identity, such as particle size, material properties, or protein oligomerisation, but also paves the way for wider exploration of biomolecular interactions and applications in nanoscience more generally.

For more details on this research and its implications, refer to the article "Single-protein optical holography" published today in Nature Photonics: https://www.nature.com/articles/s41566-024-01405-2.